This invention relates to a controlled absorption pharmaceutical formulation and, in particular, to a controlled absorption quinidine formulation which is suitable for once daily administration.
Quinidine is a cardiac depressant which reduces cardiac activity by directly depressing the excitability of the myocardium and prolonging the refractory period of cardiac muscle, thereby reducing the rate at which successive contractions take place.
Quinidine((+)-.alpha.-(6-methoxyquinolin-4-yl)-.alpha.-(5-vinylquinuclidin- 2-yl)methanol) is normally used in the form of a salt thereof, for example, quinidine gluconate or quinidine sulphate.
Quinidine sulphate is usually rapidly absorbed from the gastro-intestinal tract and peak plasma concentrations are reached in about two hours. About 60% of quinidine in the blood is bound to plasma albumin. Quinidine is almost entirely excreted in the urine; 10-50% is eliminated unchanged within 24 hours of a dose being taken. The half-life of quinidine sulphate is found to be about 6.5 hours in normal subjects.
Quinidex Extentabs (Trade Mark) is a sustained action tablet formulation of quinidine sulphate suitable for twice daily administration. To-date no controlled action quinidine formulation exists which is suitable for once daily administration and which has a high and invariable absorption profile.
It is an object of the present invention to provide a controlled adsorption form of quinidine which is suitable for once daily administration, which is characterised by a high degree of absorption, which is substantially invariable from subject to subject, and by significant plasma levels of quinidine which are maintained for an extended period after administration relative to other sustained release forms of the drug.